There is no tried and true way to know your cel is definitely production and not fake unless you're there to watch it be filmed and then steal it. However, there are ways to be reasonably certain and there are signs that a cel is fake.

The best way is to buy from a trusted seller. If you can trust your seller, you can trust your cel. Furthermore, if the cel turns out to be fake, a legitimate trustworthy dealer would take it back and refund you rather than risk their reputation.

You should try to check your cel versus what is on screen. Find the exact
frame on your LD/DVD and look for minute differences. Your cel should
probably extend past what you can see on film by at least an inch or so. It
can be quite amazing how much of a cel does not get on screen. Sometimes
people making fakes forget to extend the image past the boundaries of what
they see or simply can't because they lack the talent to do so.

In general it is unlikely your average cel you find on the net is a fake unless already marked as such. Most of them are probably not worth someone faking.

Here are some signals that could mean your cel is a fake. Note, having just
one 'symptom' is probably not biggie. Furthermore, not having symptoms isn't
a 100% guarantee. A fraudulent individual who has done his research will
probably know to include markings that a production cel would have.
Furthermore, as some fakes may be made by professional animators, it becomes
all the more difficult. Unless you have reason to believe the cel might be
fake already (outrageously good deal, suspicious seller, etc)

How are the lines on your cel? Are they photocopies? Are they extra thick
where they should be thin? Are they wobbly?
Many people have difficulty creating lines correctly when they are not
professionals, this may signal.

How are the colors? These can be hard to check indeed but are often a tip
off. It is especially difficult because scanners produce colors differently
and the colors will appear different on most people's monitors. Check how the
colors look with respect to each other.

How big is the image? Is it a hanken image for a big CD cover on a standard
sized piece of acetate? This is unlikely. Is the image 'cut off' or lacking
sufficient area over what appeared on the original? This is highly unlikely.
I've found cut off to be one of the tip offs that's more likely to be found
and easier to catch.

As a side note, having the douga, background, or a sequence number does not
necessarily mean the cel is real. Sequence numbers are fairly easy to add.
If the fraudulent person has not done their research, they may add the wrong
sequence number, so if it is way off of what it appears it should be on film,
you might want to give it a further look. As for douga and background,
sometimes the fake cel is made from the real douga! The fraudulent person
keeps the original or gains the douga through other means and creates the fake
cel.

Should you worry? For the most part, no. Fake cels are not all that common
and if you're buying cels at such an expensive level where the prices would be
enticing to those who would create fakes, it's definitely worth it to just go
with dealers you can trust. Bottom line: Buying from trustworthy dealers is
the best way you can guard against fake cels.